This project is an interdisciplinary research effort involving radiation biology, radiation physics, radiation oncology, medical oncology, and immunology relating to the clinical evaluation of new targeting molecules, including genetically engineered antibodies, antibody fragments and fusion proteins, for the selective delivery of radioactive isotopes, toxins or immunologic attack mechanisms. Initial clinical protocols currently underway include the use of intraperitoneal 177Lu- labeled CC49 by intraperitoneal infusion, in the presence of varying amounts of taxol (radiosensitizer), in the treatment of recurrent ovarian cancer (modest tumor burden). Additional clinical protocols are examining the use of total body irradiation plus I31I-radiolabeled antibodies utilizing autologous stem cell support to explore marrow ablative dosage regimens in prostate and breast carcinoma. This program will shortly initiate studies to examine monoclonal antibodies to EGF receptor, in combination with external beam radiation for the treatment of head and neck cancer. These studies include both toxicity, clinical efficacy, pharmacokinetics, immunogenicity, and tissue localization components, in order to scientifically evaluate the efficacy or shortcomings of these strategies. We will be further evaluating other new targeting agents for inclusion into future phase I and phase II clinical trials.